Objective:Cytomegalovirus (CMV) is a frequent opportunistic viral pathogen in patients with AIDS leading to retinitis and other serious manifestations. CMV disease may be successfully treated. Prophylactic antiviral therapy has been shown to reduce the risk of CMV disease if initiated early. We evaluated PCR and the antigenemia test as methods for early detection of CMV disease.Methods:Two-hundred HIV-seropositive subjects with CD4 T-cell counts below 100 × 106/l were monitored with CMV polymerase chain reaction (PCR), the antigenemia test, blood cultures and CMV immunoglobulin (Ig) G and IgM titres every second month for 1 year.Results:Thirty-eight patients (19%) developed CMV disease. The PCR test detected CMV DNA a median of 46 days before onset of disease. This was earlier than the median of 34 days for the antigenemia test and a median of 1 day for CMV blood cultures. Univariate analysis showed that the CMV PCR, the antigenemia test and blood cultures all had significant predictive values for subsequent development of CMV disease with odds ratios (OR) of 30, 22 and 20. CMV serology had no predictive value. Multivariate analysis showed that the PCR method was superior to the other tests; OR: CMV PCR 10.0, antigenemia test 4.4 and CMV cultures 4.3. No clinical parameters had any significant predictive value in the stepwise multivariate model.Conclusions:The CMV PCR and the CMV antigenemia tests are both sensitive methods that may predict development of CMV disease up to several months prior to clinical disease. These methods make it possible to select patients at high risk for CMV disease and suitable for prophylactic therapy against CMV.